Hydrochloric Acid → 1-(4-chloro-2,3-dihydro-1H-inden-1-yl)-2-oxo-N-(pyridin-4-yl)-1,2-dihydropyridine-3-carboxamide

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Reaction Steps

To a mixture of 1-(4-amino-2,3-dihydro-1H-inden-1-yl)-2-oxo-N-(pyridin-4-yl)-1,2-dihydropyridine-3-carboxamide (600 mg, 1.0 eq) in H2O (4 mL) and conc. HCl (2 mL) was added dropwise NaNO2 (1.1 eq) in H2O (1 mL) at 0° C., the mixture was stirred at room temperature for 30 minutes. Then this mixture was added to another flask containing CuCl (1.5 eq), 2 mL H2O and 1 mL aqueous HCl at 0° C., the mixture was stirred for 5 h. At the end of reaction, saturated Na2CO3 aqueous was added to adjust to pH 12. The aqueous solution was extracted with ethyl acetate three times. The combined organic layer was washed with brine and dried over MgSO4, evaporated the filtrate to give the crude product, which was purified by Flash Column (DCM:MeOH=30:1) to afford 1-(4-chloro-2,3-dihydro-1H-inden-1-yl)-2-oxo-N-(pyridin-4-yl)-1,2-dihydropyridine-3-carboxamide (350 mg, 55%). MS (ESI) 366.0 (M+H); 1H NMR (300 MHz, CDCl3) δ 12.31 (s, 1H), 8.61 (bd, 1H), 8.53 (bs, 2H), 7.69 (bs, 2H), 7.38 (bd, 1H), 7.26 (bm, 2H), 7.03 (d, J=6.0 Hz, 2H), 6.69 (bs, 1H), 6.46 (bs, 1H), 3.05-3.25 (bm, 2H), 2.91 (bd, 1H), 2.08 (bd, 1H).

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